Profile of MicroRNAs Differentially Produced in Hearts from Patients with Hypertrophic Cardiomyopathy and Sarcomeric Mutations

Palacín, María; Reguero, Julián R.; Martı́n, M. J.; Molina, Beatriz Díaz; Morı́s, César; Álvarez, Victoria; Coto, Eliécer

doi:10.1373/clinchem.2011.168005

Cited by 29 publications

(19 citation statements)

References 5 publications

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“…Two earlier studies reported that miR-1 was the most-abundant cardiac microRNA, comprising almost 40% of total microRNA in the adult mouse heart (45,46). Two recent studies did not confirm this finding (47,48). We find by deep sequencing and RT-qPCR that miR-1 is one of the most-abundant, but not the principal, microRNA in adult mouse hearts.…”

Section: Discussioncontrasting

confidence: 51%

Epitranscriptional orchestration of genetic reprogramming is an emergent property of stress-regulated cardiac microRNAs

Matkovich

Hecker

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Cardiac stress responses are driven by an evolutionarily conserved gene expression program comprising dozens of microRNAs and hundreds of mRNAs. Functionalities of different individual microRNAs are being studied, but the overall purpose of interactions between stress-regulated microRNAs and mRNAs and potentially distinct roles for microRNA-mediated epigenetic and conventional transcriptional genetic reprogramming of the stressed heart are unknown. Here we used deep sequencing to interrogate microRNA and mRNA regulation in pressure-overloaded mouse hearts, and performed a genome-wide examination of microRNA-mRNA interactions during early cardiac hypertrophy. Based on abundance and regulatory patterns, cardiac microRNAs were categorized as constitutively expressed housekeeping, regulated homeostatic, or dynamic early stress-responsive microRNAs. Regulation of 62 stressresponsive cardiac microRNAs directly affected levels of only 66 mRNAs, but the global impact of microRNA-mediated epigenetic regulation was amplified by preferential targeting of mRNAs encoding transcription factors, kinases, and phosphatases exerting amplified secondary effects. Thus, an emergent cooperative property of stress-regulated microRNAs is orchestration of transcriptional and posttranslational events that help determine the stress-reactive cardiac phenotype. This global functionality explains how large endorgan effects can be induced through modest individual changes in target mRNA and protein content by microRNAs that sense and respond dynamically to a changing physiological milieu.microRNA-mRNA interactome | transcriptome regulation | systems biology

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Section: Discussioncontrasting

confidence: 51%

Epitranscriptional orchestration of genetic reprogramming is an emergent property of stress-regulated cardiac microRNAs

Matkovich

Hecker

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…These three factors might combine to skew the results of this study towards higher apparent MIAME compliance than actually exists in the wider literature, so I examined publications that appeared in journals other than the top four publishers during a two-week period in August/September, 2011. This period, subsequently referred to as “2 weeks”, was centered on the September 2 publication date of a Clinical Chemistry miRNA microarray profiling report (24). …”

Section: Resultsmentioning

confidence: 99%

Data Submission and Quality in Microarray-Based MicroRNA Profiling

Witwer

2013

Clinical Chemistry

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Background Public sharing of scientific data has assumed greater importance in the ‘omics’ era. Transparency is necessary for confirmation and validation, and multiple examiners aid in extracting maximal value from large datasets. Accordingly, database submission and provision of the Minimum Information About a Microarray Experiment (MIAME) are required by most journals as a prerequisite for review or acceptance. Methods In this study, the level of data submission and MIAME compliance was reviewed for 127 articles that included microarray-based microRNA profiling and that were published from July, 2011 through April, 2012 in the journals that published the largest number of such articles—PLOS ONE, the Journal of Biological Chemistry, Blood, and Oncogene—along with articles from nine other journals, including Clinical Chemistry, that published smaller numbers of array-based articles. Results Overall, data submission was reported at publication for less than 40% of all articles, and almost 75% of articles were MIAME-noncompliant. On average, articles that included full data submission scored significantly higher on a quality metric than articles with limited or no data submission, and studies with adequate description of methods disproportionately included larger numbers of experimental repeats. Finally, for several articles that were not MIAME-compliant, data re-analysis revealed less than complete support for the published conclusions, in one case leading to retraction. Conclusions These findings buttress the hypothesis that reluctance to share data is associated with low study quality and suggest that most miRNA array investigations are underpowered and/or potentially compromised by a lack of appropriate reporting and data submission.

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“…Our results suggest that there could be an inter-relation between MYH7 gene mutation and miR-29a levels as well as and between MYBPC3 gene mutation and miR-155 levels. Indeed, a link between miRNAs and a mutation in the MYH7 gene was already shown in tissues of patients with hypertrophic cardiomyopathies [20]. …”

Section: Discussionmentioning

confidence: 99%

Blood-based microRNA signatures differentiate various forms of cardiac hypertrophy

Derda¹,

Thum²,

Lorenzen³

et al. 2015

International Journal of Cardiology

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Background Hypertrophic cardiomyopathy (HCM) is caused by mutations in different structural genes and induces pathological hypertrophy with sudden cardiac death as a possible consequence. HCM can be separated into hypertrophic non-obstructive and obstructive cardiomyopathy (HNCM/HOCM) with different clinical treatment approaches. We here distinguished between HNCM, HOCM, cardiac amyloidosis and aortic stenosis by using microRNA profiling and investigated potential interactions between circulating miRNA levels and the most common mutations in MYH7and MYBPC3 genes. Methods Our study included 4 different groups: 23 patients with HNCM, 28 patients with HOCM, 47 patients with aortic stenosis and 22 healthy controls. Based on previous findings, 8 different cardiovascular known microRNAs (miR-1, miR-21, miR-29a, miR-29b, miR-29c, miR-133a, miR-155 and miR-499) were studied in serum of all patients and compared with clinically available patient data. Results We found miR-29a levels to be increased in patients with HOCM and correlating markers of cardiac hypertrophy. This was not the case in HNCM patients. In contrast, we identified miR-29c to be upregulated in aortic stenosis but not the other patient groups. ROC curve analysis of miR-29a/c distinguished between HOCM patients and aortic stenosis patients. MiR-29a and miR-155 levels discriminated HNCM patients from patients with senile cardiac amyloidosis. MiR-29a increased mainly in HOCM patients with a mutation in MYH7, whereas miR-155 was decreased in hypertrophic cardiomyopathy patients with a mutation in MYBPC3. Conclusion We demonstrated that miR-29a and miR-29c show a specific signature to distinguish between aortic stenosis, hypertrophic non-obstructive and obstructive cardiomyopathies and thus could be developed into clinically useful biomarkers.

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Profile of MicroRNAs Differentially Produced in Hearts from Patients with Hypertrophic Cardiomyopathy and Sarcomeric Mutations

Cited by 29 publications

References 5 publications

Epitranscriptional orchestration of genetic reprogramming is an emergent property of stress-regulated cardiac microRNAs

Epitranscriptional orchestration of genetic reprogramming is an emergent property of stress-regulated cardiac microRNAs

Data Submission and Quality in Microarray-Based MicroRNA Profiling

Blood-based microRNA signatures differentiate various forms of cardiac hypertrophy

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